Vol 13, No 4-5 (2016)

HIV/AIDS is one of the most important problems of world health care. Number of HIV infected individuals in the world are about 40 millions and continue rising. Fight against HIV/AIDS is one of United Nations’ «Millenium Goals». Efforts of many research institutions and unprecedented financial resources are mobilized for counteraction of the disease. Despite intensive investigations there are no radical treatment or effective preventive vaccine, which is able to protect vulnerable populations from HIV infection. The key steps of HIV/AIDS investigations, development of drugs and strategies of prevention and treatment of the disease, and also perspectives of epidemic control are reviewed.

Background. The purpose of this study was to characterize the immunologic properties of the monomeric allergoid obtained from house dust mite Dermatophagoides pteronyssinus (D. pteronyssinus) extract. Methods. To obtain monomeric allergoid the extract from D. pteronyssinus (D1) was chemically modified by succinilation and then the degree of modification and total protein content were determined. Analysis of proteins in native D1 or modified sD1 was performed by SDS-PAGE. Determination of the major allergen Der p 1 in the native extract D1 was done by mass-spectrometry method. For measurement of tertiary structure alterations of protein molecules in D1 or recombinant Der p 1 (rDer p 1) after their modification by succinilation the circular dichroism (CD) method was applied. Allergenicity of sD1 was estimated by inhibition of specific IgE binding in ELISA and chemiluminescent analysis using Phadia ImmunoCAP as well as by detection of histamine released from leukocytes of whole blood of Der p sensitized patients after its incubation with D1 or sD1. To evaluate immunogenicity of D1 and sD1 BALB/c mice were i.p. immunized 4 times in 3 week interval with D1 or sD1 with or without adjuvant Al(OH),. The levels of anti-Der p IgE, IgG1 and IgG2a in pulled mice sera were determined by ELISA. Results. Succinilation of D1 extract led to «unfolding» of allergen molecules in modified sD1. The degree ofmodification was 98,9%. Results of SDS-PAGE demonstrated that native D1 and succinilated sD1 extract showed bands at the same molecular mass confirming that succinilation does not influence the size of modified molecule which thus maintains the monomeric nature of the sD1. Mass-spectrometry analysis revealed the presence of major allergen Der p 1 in the native D1 extract. CD method demonstrated the alteration of tertiary structure of succinilated recombinant rDer p 1 that may be extrapolated on the other allergenic proteins in the sD1 extract. Allergenicity of sD1 was significantly reduced in compare to D1 that was confirmed by inhibition of IgE-binding and histamine release from leukocytes of whole blood, Immunization of BALB/c mice with sD1 (with or without Al(OH)3) induced anti-Der p IgE-response which was substantially lower than that of D1 induced. At the same time anti-Der p IgG1 and IgG2a responses after immunization with sD1 (with or without Al(OH)3) were significantly higher than that ofD1 induced. Conclusion. Modification of the extract from house dust mite D. pteronyssinus by succinilation leads to formation of monomeric allergoid possesses low allergenicity and preserved (or even increased) immunogenicity that may a new approach for creation of allergy vaccines for safe and effective allergen-specific immunotherapy.

Asthma is a widespread, phenotypically heterogeneous, chronic disease characterized by inflammation and airflow obstruction, bronchial hyperresponsiveness and recurrent symptoms of respiratory discomfort. On the one hand, the treatment of asthma is based on the determination of the severity and on the control of symptoms. On the other hand, it is based on the risk management of exacerbations. The control of asthma in most patients is achieved as a result of conventional treatment with inhaled corticosteroids or a combination of them with long-acting beta-2-agonists. However, a substantial proportion of patients with difficult asthma phenotypes (severe atopic asthma, asthma and obesity, smoker’s asthma, asthma in the elderly, asthma with fixed airflow obstruction) can be refractory to the conventional therapy. Additional therapy with the long-acting anticholinergic drug such as tiotropium can optimize the control in these patients. This article describes the complex phenotypes of asthma and the clinical cases of tiotropium efficacy in therapy of such patients.

In the article the principal approaches to immune analyses depending on various clinical situations are dicussed.

Common variable immunodeficiency (CVID) is the most prevalent clinically important form of primary immunodeficiencies (PID). CVID is characterized by a wide variability of complications which can affect almost all organs and systems. Infectious complications are more typical, but non-infectious complications, in particular granulomatous lymphocytic interstitial lung disease (GLILD), have more strong influence on the course, prognosis and severity of the disease and the patient’s quality of life. GLILD is a challenge not only from a diagnostic point of view (manifestations are often misdiagnosed and treated as sarcoidosis, tuberculosis, lymphoproliferative disease), but also in terms of treatment strategy selection. Rituximab - is one of the most promising methods of GLILD therapy, which showed its efficiency in limited clinical observations. A clinical case of successful treatment of GLILD associated with CVID, using rituximab on the background of a regular replacement immunotherapy with immunoglobulin for intravenous administration (IVIG) is described in this article.

One of the most common problems in basic treatment of allergic rhinoconjunctivitis (ARC) is concomitant viral infection. In these cases antiviral and immunomodulatory medications adding to the therapy could be useful. Recent data showed clinical efficacy of a new medication - allergoferon (recombinant human interferon α -2b + loratadine) in ARC treatment. The pharmacological action of allergoferon is achieved due to its antihistaminic, anti-itching, anti-exudative, anti-inflammatory, immunomodulatory, and antiviral properties. In this study clinical efficacy and safety of allergoferon in the treatment of allergic rhinoconjunctivitis has been shown.